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Table 2 The strengths and weaknesses of various safety strategies of CAR-T cells

From: Next generation chimeric antigen receptor T cells: safety strategies to overcome toxicity

Safety strategy Strengths Weaknesses
Suicide switch HSV-TK 1. powerful effect 2. extensive clinical experience 1. immunogenicity 2. clinical incompatibility 3. slow onset 4. no preventive effect for toxicity 5. premature eradication of CAR-T cells
iCasp9 1. no immunogenicity 2.clinical compatibility 2. rapid onset 1. no preventive effect for toxicity 2. premature eradication of CAR-T cells
CD20 1. no immunogenicity 2. rapid onset 1. antibody biodistribution 2. on-target toxicity from antibody 3. prodrug infusion reaction 4. no preventive effect for toxicity 5. premature eradication of CAR-T cells
EGFRt 1. no immunogenicity 2. rapid onset 3. in vivo tracking 1. antibody biodistribution 2. on-target toxicity from antibody 3. prodrug infusion reaction 4. no preventive effect for toxicity 5. premature eradication of CAR-T cells
Endogenous switch synNotch 1. control the expression of the CARs 2. Specific recognition of tumor sites 1. uncontrolled activation of CAR-T cells 2. the choice of two antigens is difficult
iCAR 1. antigen-selectively regulate T cell responses 2. protect normal tissue from CAR-T cells 1. uncontrolled activation of CAR-T cells 2. potential “on-target, off-tumor” effect
Combinatorial Target-Antigen Recognition 1. precise killing of CAR-T cells 2. overcome antigen loss 1. uncontrolled activation of CAR-T cells 2. the choice of two antigens is difficult 3. potential “on-target, off-tumor” effect
Exogenous switch Bispecific T Cell Engager 1. controlled activation of CAR-T cells 2. simplify manufacturing of CAR-T cells 1. The choice of small molecules needs more consideration
On-switch CAR 1. controlled activation of CAR-T cells 1. The choice of small molecules needs more consideration